A Thermophilic Bacterial Esterase for Scavenging Nerve Agents: A Kinetic, Biophysical and Structural Study

Organophosphorous nerve agents (OPNA) pose an actual and major threat for both military and civilians alike, as an upsurge in their use has been observed in the recent years. Currently available treatments mitigate the effect of the nerve agents, and could be vastly improved by means of scavengers of the nerve agents. Consequently, efforts have been made over the years into investigating enzymes, also known as bioscavengers, which have the potential either to trap or hydrolyze these toxic compounds. We investigated the previously described esterase 2 from Thermogutta terrifontis (TtEst2) as a potential bioscavenger of nerve agents. As such, we assessed its potential against G-agents (tabun, sarin, and cyclosarin), VX, as well as the pesticide paraoxon. We report that TtEst2 is a good bioscavenger of paraoxon and G-agents, but is rather slow at scavenging VX. X-ray crystallography studies showed that TtEst2 forms an irreversible complex with the aforementioned agents, and allowed the identification of amino-acids, whose mutagenesis could lead to better scavenging properties for VX. In conjunction with its cheap production and purification processes, as well as a robust structural backbone, further engineering of TtEst2 could lead to a stopgap bioscavenger useful for in corpo scavenging or skin decontamination.

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Structural Study of Asymmetric Autocatalysis by X-Ray Crystallography

Advances in Asymmetric Autocatalysis and Related Topics ◽

10.1016/b978-0-12-812824-4.00010-1 ◽

2017 ◽

pp. 183-202 ◽

Cited By ~ 1

Author(s):

Arimasa Matsumoto ◽

Tsuneomi Kawasaki ◽

Kenso Soai

Keyword(s):

Structural Study ◽

X Ray ◽

X Ray Crystallography ◽

Asymmetric Autocatalysis

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Structural Studies by NMR and X-Ray Crystallography of N-(p-Toluenesulfonyl)-Amino Acids

Structural Chemistry ◽

10.1023/b:stuc.0000021530.95903.8e ◽

2004 ◽

Vol 15 (3) ◽

pp. 215-221 ◽

Cited By ~ 9

Author(s):

Liliana Aguilar-Castro ◽

Margarita Tlahuextl ◽

Antonio R. Tapia-Benavides ◽

José Guadalupe Alvarado-Rodríguez

Keyword(s):

Amino Acids ◽

Structural Studies ◽

X Ray ◽

X Ray Crystallography

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Synthesis of [F3S⋮NXeF][AsF6] and Structural Study by Multi-NMR and Raman Spectroscopy, Electronic Structure Calculations, and X-ray Crystallography

Inorganic Chemistry ◽

10.1021/ic061899+ ◽

2007 ◽

Vol 46 (4) ◽

pp. 1369-1378 ◽

Cited By ~ 29

Author(s):

Gregory L. Smith ◽

Hélène P. A. Mercier ◽

Gary J. Schrobilgen

Keyword(s):

Raman Spectroscopy ◽

Electronic Structure ◽

Structural Study ◽

Electronic Structure Calculations ◽

X Ray ◽

X Ray Crystallography ◽

Structure Calculations

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Synthesis and Characterization of Various Amino Acid Derived Thiohydantoins

Proceedings ◽

10.3390/ecsoc-22-05690 ◽

2018 ◽

Vol 9 (1) ◽

pp. 37

Author(s):

Petar Stanić ◽

Marija Živković ◽

Biljana Šmit

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Allyl Isothiocyanate ◽

Structural Diversity ◽

Biologically Active ◽

Reaction Conditions ◽

X Ray ◽

X Ray Crystallography ◽

Sulfur Containing

Hydantoins and their sulfur containing analogues, thiohydantoins, are cyclic ureides that have attracted huge attention ever since their discovery. Most of them are biologically active compounds and several points of structural diversity have made them very synthetically attractive. Although substituents can be introduced to the hydantoin nucleus, most substituted hydantoins are synthesized from substrates already containing these groups, while forming the hydantoin nucleus. This is a common route to the synthesis of hydantoins and one of them is employed in this study. A series of 3-allyl-2-thiohydantoins is synthesized from various α-amino acids in a reaction with allyl isothiocyanate. The substitution of the acquired thiohydantoin depends on the structure of the starting α-amino acid. The residual group of the α-amino acid becomes the substituent at the C5-position, while N-monosubstituted amino acids give rise to a substituent in the N1-position. The reaction is carried out in a two-step process and the reaction conditions generally depend on the nature of the amino acid itself. All thiohydantoins are obtained in a good yield and fully characterized by NMR and IR spectroscopy, as well as X-ray crystallography.

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Crystal structure of glycosyltrehalose synthase fromSulfolobus shibataeDSM5389

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x1801453x ◽

2018 ◽

Vol 74 (11) ◽

pp. 741-746

Author(s):

Nobuo Okazaki ◽

Michael Blaber ◽

Ryota Kuroki ◽

Taro Tamada

Keyword(s):

Crystal Structure ◽

Amino Acids ◽

Catalytic Mechanism ◽

Catalytic Domain ◽

Structural Basis ◽

Hyperthermophilic Archaeon ◽

X Ray ◽

X Ray Crystallography ◽

Sulfolobus Shibatae ◽

Glucosidic Bond

Glycosyltrehalose synthase (GTSase) converts the glucosidic bond between the last two glucose residues of amylose from an α-1,4 bond to an α-1,1 bond, generating a nonreducing glycosyl trehaloside, in the first step of the biosynthesis of trehalose. To better understand the structural basis of the catalytic mechanism, the crystal structure of GTSase from the hyperthermophilic archaeonSulfolobus shibataeDSM5389 (5389-GTSase) has been determined to 2.4 Å resolution by X-ray crystallography. The structure of 5389-GTSase can be divided into five domains. The central domain contains the (β/α)8-barrel fold that is conserved as the catalytic domain in the α-amylase family. Three invariant catalytic carboxylic amino acids in the α-amylase family are also found in GTSase at positions Asp241, Glu269 and Asp460 in the catalytic domain. The shape of the catalytic cavity and the pocket size at the bottom of the cavity correspond to the intramolecular transglycosylation mechanism proposed from previous enzymatic studies.

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